Westermark P, Engström U, Westermark G T, Johnson K H, Permerth J, Betsholtz C
Department of Pathology, University of Linköping, Sweden.
Diabetes Res Clin Pract. 1989 Sep 18;7(3):219-26. doi: 10.1016/0168-8227(89)90008-9.
Islet amyloid polypeptide (IAPP) is a 37-amino-acid putative hormone which is expressed by islet B-cells and most probably is co-released with insulin. IAPP is synthesized as an 89-amino-acid prepropeptide in which IAPP is flanked by two short peptides. The two short peptides are ultimately cleaved off at basic residues. In the present study, we used antisera to three different synthetic peptides corresponding to positions 18-30, 40-50 and 53-62 of prepro-IAPP. The two latter peptides fall within the mature IAPP molecule while the first peptide corresponds to the N-terminal flanking peptide. We demonstrate that normal B-cells and islet amyloid both react immunohistochemically with all of these antisera. Using the immunogold labelling technique, we also demonstrate electron microscopically that both the IAPP immunoreactivity and the pro1-IAPP immunoreactivity in amyloid deposits are confined to the amyloid fibrils per se. These data indicate that not only mature IAPP but also the N-terminal flanking peptide is present in islet amyloid deposits. It remains to be shown if the propeptide segments are involved in the pathogenesis of these amyloid depositions.
胰岛淀粉样多肽（IAPP）是一种由胰岛β细胞表达的含37个氨基酸的假定激素，很可能与胰岛素共同释放。IAPP最初被合成为一种含89个氨基酸的前体肽原，其中IAPP两侧各有一段短肽。这两段短肽最终在碱性残基处被切除。在本研究中，我们使用了针对前体IAPP第18 - 30、40 - 50和53 - 62位氨基酸的三种不同合成肽的抗血清。后两种肽位于成熟IAPP分子内，而第一种肽对应于N端侧翼肽。我们证明正常β细胞和胰岛淀粉样物质在免疫组织化学上均与所有这些抗血清发生反应。使用免疫金标记技术，我们还通过电子显微镜证明淀粉样沉积物中的IAPP免疫反应性和前体IAPP免疫反应性均局限于淀粉样纤维本身。这些数据表明，不仅成熟的IAPP，而且N端侧翼肽也存在于胰岛淀粉样沉积物中。前体肽段是否参与这些淀粉样沉积的发病机制仍有待确定。
